Analgesic and Anti-inflammatory Effects of Xueshan Jinluohan Coating Agent and Its Transdermal Mechanism

Topical traditional Chinese medicine (TCM) preparations are widely used for the management of inflammatory and pain-related conditions because they provide local therapeutic effects while potentially reducing systemic adverse reactions. However, the pharmacodynamic characteristics and transdermal mechanisms underlying many clinically applied formulations remain insufficiently characterized. Xueshan Jinluohan Pain-Relieving Coating Agent (XJCA), a Tibetan medicine formulation, is commonly prescribed for inflammatory pain, yet the influence of application area, duration of action, and the relative contributions of local versus systemic effects have not been systematically evaluated. This study establishes an integrated in vivo-in vitro methodological framework to investigate these parameters. Multiple complementary animal models were employed to assess central and peripheral analgesic activity and acute inflammatory responses, enabling evaluation of area-, time-, and local-versus-systemic-dependent effects. In parallel, a Franz diffusion cell system coupled with ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to characterize the percutaneous absorption kinetics of two principal alkaloids, benzoylaconine and aconitine. XJCA demonstrated significant area- and time-dependent analgesic and anti-inflammatory effects, and larger application areas were associated with greater systemic contribution to analgesic efficacy. Transdermal kinetic analysis revealed that benzoylaconine exhibited a substantially higher steady-state flux and followed diffusion-controlled release consistent with the Higuchi model, whereas aconitine showed lower permeability and a more complex release profile. These findings link transdermal delivery behavior with observed pharmacodynamic outcomes and provide a structured framework for evaluating and optimizing topical TCM formulations.